This invention relates to a method for the prevention and reduction of foam in fermentation broths. More particularly, it relates to such a method wherein the foam is controlled by the addition of chemical agents. Foams occur as an undesirable incidental feature in many systems. Although some theories of foam formation have been proposed, little is known about why some compounds are antagonistic to foams while others are not. Of considerable frustration to those in the art of foam control is the fact that each foam control problem is unique, calling for a different compound for effective foam control. Some materials are useful only to prevent foam formation ("antifoams") while some are useful only to reduce foam which has already formed ("defoamers"). Efforts to predict which compound will work in a given system have not proven successful. As a result, foam control is basically an empirical art.
The following quotations summarize the views of experts in the field of foam control:
"More than 300,000 chemicals are now available, thousands of which work as defoamer ingredients in particular systems. It is difficult then to pinpoint exactly which defoamer will work where, and why, so it is best to leave the problem to specialists. Another reason is that all variables must be considered when formulating defoamers compatible with production systems." PA0 Foam Control, A Misunderstood Concept, by Marshall Ott, Household & Personal Products Industry, February 1978. PA0 "Because of the variety of materials to be defoamed and the extreme conditions of operation, no single material has universal application as a chemical antifoam. Some systems are predominantly aqueous, whereas others are organic mixtures with only a trace of moisture; in others the presence or absence of solids may be a factor. Operational conditions vary from high pressure steam generation to vacuum distillation; jet fuels may foam on the plane's ascent, and low-boiling substances may cause foaming in the oil-well pumping of certain gaseous petroleum crudes. To add to the difficulties, the antifoam for one system may be a foamer in another." (Emphasis added). PA0 Encyclopedia of Polymer Science and Technology, Vol. 2, 1964, pg. 164 (Antifoaming Agents). PA0 "Thus a paper mill may easily use six or more defoamers for routine coated paper manufacture. The same holds true for other defoamer applications. For example, a paint manufacturer may need different defoamers for the various phases of paint production such as in the pigment grind, letdown, can filling, and mill effluent. Manufacturers of textiles, sugar from sugar beets, and fertilizers require different defoamers for the various phases of production." PA0 Encyclopedia of Chemical Technology, Vol. 7, 1979, pg. 433 (Defoamers). PA0 "One of the fruits of success in this endeavor would be to diminish the empiricism that at present characterizes the search for an optimum foam inhibitor." PA0 Mechanisms of Foam Stabilization and Antifoaming Action, by S. Ross, Rensselaer Polytechnic Institute, Chemical Engineering Progress. Vol. 63, #9, pg. 46. PA0 "It is well known that the performance of an antifoam or foam preventer is strongly dependent on the type of foaming system involved. However, little is known about the specific parameters which influence antifoaming activity." PA0 Mechanism of Antifoaming Action, by R. D. Kulkarni et al, J. of Colloid and Interface Science, Vol. 59, #3, May 1977. PA0 "An important problem of commercial aerobic fermentation processes consists of the foaming of media, and the suppression of this tendency. In the fermentation of antibiotics it is particularly important to choose the correct method for the suppression of foaming, and to choose a suitable anti-foam agent." PA0 The Foams of Fermentation Broths, by Laszlo Szarka, Biotechnology & Bioengineering, Vol. XI, pg. 701, 1969. PA0 "are useful in controlling foams in many different types of systems. They control foam encountered in gas-treating systems in which a mixture of glycols and alkanolamines is used to dehydrate and purify natural gas; in activated-sludge-process sewerage plants, particularly in aeration basins and elsewhere; in protein adhesives solutions, such as casein and soybean adhesives as used in the plywood industry; in latex adhesives, printing inks; aqueous emulsions paints; etc."
Foaming in fermentation broths is particularly problematic in that the material chosen must be compatible with sterilization procedures, non-toxic to the fermentation organism, non-interfering with extract of the desired fermentation product, as well as be an effective foam control agent. In particular, the pharmaceutical industry has a long-felt need for more effective foam control agents.
From a technical standpoint there are a large number of instances where silicone foam control agents are preferred because of their superior performance. However, since silicones are often 3 to 10 times more expensive than other foam control compounds, the non-silicones are economically preferred, even if their performance is inferior. Therefore, it would be desirable to provide a highly effective and economical foam control agent suitable for use in fermentation broths.
Suppression of foams in fermentation broths is known. Examples of typically used compounds include silicone emulsions, silica dispersions, pure silicone fluids, polypropylene glycol, and various block copolymers of propylene oxide and ethylene oxide.
U.S. Pat. No. 3,862,243 (Bellos - Petrolite) discloses compounds of the general formula EQU ZO(EtO).sub.e (BuO).sub.m H
where Z is a hydrocarbon group, EtO is an ethoxy moiety, BuO is a butoxy moiety, e is from 3 to 30 and m is from 2 to 20. This patent teaches that these compounds
Similar to the teachings of the above patent, commercial products are available which have the general formula EQU ZO(EtO).sub.e (PrO).sub.p H
wherein PrO is a propoxy moiety, p is from 5 to 50, and the other symbols are as defined above. These compounds are sold as antifoams for detergent systems such as dishwashing detergents, rinse aids, and metal spray cleaning detergent compounds; caustic scrubbers; fermentation broths and rolling oil formulations.
Numerous other polyalkoxylated compounds are also known and many of these compounds are known to be useful as foam control agents, albeit in systems far removed from fermentation broths. For example, a form of the composition found to be useful in the present invention for control of foam in fermentation broth has seen limited use as a defoamer in the adhesives industry. However, there has been no teaching or suggestion of its applicability to the radically different field of fermentation processes, especially with respect to the distinctive fermentation broths. Thousands of foam control agents exist, each of which is effective with respect to certain systems, and even those found to be effective in a particular system often are effective only as to certain conditions for that system. Thus, there has been no indication that such compositions, out of thousands of possibilities, would be satisfactory defoamers for fermentation broths.